Calcium phosphates (CaP) and in particular hydroxyapatite (Ca10(PO4)6(OH)2, HA), is a mineral that is widely used in medical applications due to its similarity to the mineral components of bone and teeth and its biocompatibility. Furthermore hydroxyapatite is non-toxic, biocompatible and bioactive. This means that hydroxyapatite is not harmful and not recognized as a foreign body and on the other hand that it may have positive effects on remodelling of bone. Hence hydroxyapatite has been widely used in bone repair and as drug/gene delivery vehicle, catalyst, ion adsorption/exchange agent, photoelectric regent, etc. Resorbable nanoparticles (i.e. particles that can be dissolved in vivo) are of special interest for a number of applications, e.g. bone void fillers, drug delivery vehicle, desensitization of dentin tubuli, etc.
Calcium phosphates, such as hydroxyapatite and tricalcium phosphate, are widely used in biomedical applications because of their good biocompatibility, bioactivity, and similarity to bone minerals. The morphology, structure, and size of calcium phosphate particles can influence the properties in their applications in hard tissue repair and regeneration, drug/gene delivery, protein adsorption, catalysis, and ion adsorption/exchange etc. Particles with spherical shape and large pore volume are good candidates for drug delivery, protein and ion adsorption, and bone and teeth fillers. So they have attracted more and more attentions recently.
Calcium phosphates, such as hydroxyapatite, spontaneously grow like flakes, fibers or rods by wet chemical methods. Spherical calcium phosphates have only been prepared using structure directing agents, such as ion substituents, surfactants and biomolecules. The present inventors showed in WO2011/016772 that strontium ions affected the morphology of calcium phosphates to form hollow spheres.
Not all morphologies are convenient to serve as delivery particles, catalyst support, ion adsorption/exchange agent, etc., until now when for example rod, tubular, sheet or spherical shaped nanoparticles have been investigated. By way of example, to make a drug delivery process efficient, high surface areas and porous structures are advantageous to adsorb as much active substance as possible and, of course, there is as well the requirement of biocompatibility and an interaction between carrier and substance.
One problem for the preparation of CaP particles is to control size distribution and shape of the particles. Often the size distribution is wide and caused by the hexagonal symmetry and the lattice parameters of CaP. Most likely an orientation along the c-axis and therewith a pin-like shape occurs.
Furthermore hollow particles that are not formed by using tedious techniques or through the use of additives or substitution ions that might jeopardize authorial approval is also wanted.